Exon deletions and variants of human estrogen receptor mRNA in endometrialhyperplasia and adenocarcinoma

Estrogen receptors (estrogen receptor alpha, ER) belong to a family of liga nd-modulated transcription factors that play an important role in the progr ession of such tumors as breast and endometrial cancers. Functional domains , a set of mutations and variants produced by internal deletions of ER mRNA , have mainly been identified in breast cancer. Experimental results sugges t that the presence of variants may result in different proteins which diff er in activity and modulate the ER signaling pathway differently. We analyzed samples from 21 cases of endometrial hyperplasia and from 29 ca ses of endometrial cancer for the presence of internal exons and exon delet ion variants of ER mRNA. ER and progesterone receptor (PgR) proteins were m easured using Western blot technique in all endometrial cancer samples. We found that absence of the wild-type exon PCR product of ER mRNA in a sam ple increased in parallel with malignant potential in both sample types, wh ereas the number of exon deletion variants detected in the same sample decr eased in eases of malignancy. The precise deletions of the respective exons suggest that they are probabl y the result of splicing errors. A relatively high number of variants in hy perplasia samples may indicate the important role of ER mRNA variants in th e physiologic regulation of transcription in estrogen-sensitive genes. Eleven of 29 adenocarcinomas expressed a 62-kDa ER protein, truncated at th e amino terminal, whereas all but one sample expressed a short 52 kDa varia nt ER protein. Our results suggest that differing ER proteins are generally present in human endometrial adenocarcinomas and that they may influence t he estradiol signaling pathways.